Project description:Remote ischemic preconditioning (RIPC) involves deliberate, brief interruptions of blood flow to increase the tolerance of distant critical organs to ischemia. This study tests the effects of limb RIPC in a porcine model of controlled hemorrhage without replacement therapy simulating an extreme field situation of delayed evacuation to definitive care. Twenty-eight pigs (47 ± 6 kg) were assigned to: (1) control, no procedure (n = 7); (2) HS = hemorrhagic shock (n = 13); and (3) RIPC + HS = remote ischemic preconditioning followed by hemorrhage (n = 8). The animals were observed for 7 h after bleeding without fluid replacement. Survival rate between animals of the RIPC + HS group and those of the HS group were similar (HS, 6 of 13[46%]-vs-RIPC + HS, 4 of 8[50%], p = 0.86 by Chi-square). Animals of the RIPC + HS group had faster recovery of mean arterial pressure and developed higher heart rates without complications. They also had less decrease in pH and bicarbonate, and the increase in lactate began later. Global oxygen delivery was higher, and tissue oxygen extraction ratio lower, in RIPC + HS animals. These improvements after RIPC in hemodynamic and metabolic status provide essential substrates for improved cellular response after hemorrhage and reduction of the likelihood of potentially catastrophic consequences of the accompanying ischemia.
Project description:Hemorrhage remains a common cause of death despite the recent advances in critical care, in part because conventional resuscitation fluids fail to prevent lethal inflammatory responses. Here, we analyzed whether ethyl pyruvate can provide a therapeutic anti-inflammatory potential to resuscitation fluids and prevent organ damage in porcine hemorrhage. Adult male Yorkshire swine underwent lethal hemorrhage with trauma and received no resuscitation treatment or resuscitation with Hextend alone, or supplemented with ethyl pyruvate. Resuscitation with ethyl pyruvate did not improve early hemodynamics but prevented hyperglycemia, the intrinsic coagulation pathway, serum aspartate aminotransferase, and myeloperoxidase in the major organs. Resuscitation with ethyl pyruvate provided an anti-inflammatory potential to restrain serum TNF and high-mobility group B protein 1 levels. Ethyl pyruvate inhibited nuclear factor [kappa]B in the spleen but not in the other major organs. In contrast, ethyl pyruvate inhibited NO in all the major organs, and it also inhibited TNF production in the major organs but in the lung and heart. The most significant effects were found in the terminal ileum where ethyl pyruvate inhibited cytokine production, restrained myeloperoxidase activity, preserved the intestinal epithelium, and prevented the systemic distribution of bacterial endotoxin. Ethyl pyruvate can provide therapeutic anti-inflammatory benefits to modulate splenic nuclear factor [kappa]B, restrain inflammatory responses, and prevent hyperglycemia, the intrinsic coagulation pathway, and organ injury in porcine hemorrhage without trauma.
Project description:The rheological properties of porcine heart, kidney, liver and brain were measured using dynamic oscillatory shear tests over a range of frequencies and shear strains. Frequency sweep tests were performed from 0.1 Hz to a maximum of 9.5 Hz at a shear strain of 0.1%, and strain sweep tests were carried out from 0.01% to 10% at 1 Hz. The effect of pre-compression of samples up to 10% axial strain was considered. The experimental measurements were fit to a Semi-Fractional Kelvin Voight (S-FKV) model. The model was then used to predict the stress relaxation in response to a step strain of 0.1%. The prediction was compared to experimental relaxation data for the porcine organ samples, and the results agreed to within 30%. In conclusion, this study measured the rheological properties of porcine organs and used a fractional viscoelastic model to describe the response in frequency and time domain.
Project description:PURPOSE:Home sleep testing devices are being widely used in diagnosis/screening for obstructive sleep apnea (OSA). We examined differences in OSA metrics obtained from two devices with divergent home monitoring strategies, the Apnea Risk Evaluation System (ARES™, multiple signals plus forehead reflectance oximetry) and the Nonin WristOx2™ (single channel finger transmission pulse oximeter), compared to differences from night-night variability of OSA. METHODS:One hundred fifty-two male/26 female subjects (BMI = 30.3 ± 5.6 kg/m2, age = 52.5 ± 8.9 years) were recruited without regard to OSA symptoms and simultaneously wore both ARES™ and Nonin WristOx2™ for two nights (n = 351 nights). Automated analysis of the WristOx2 yielded oxygen desaturation index (ODIOx2, ?4% O2 dips/h), and automated analysis with manual editing of ARES™ yielded AHI4ARES (apneas + hypopneas with ?4% O2 dips/h) and RDIARES (apneas + hypopneas with ?4% O2 dips/h or arousal surrogates). Baseline awake oxygen saturation, percent time < 90% O2 saturation (%time < 90%O2Sat), and O2 signal loss were compared between the two methods. RESULTS:Correlation between AHI4ARES and ODIOx2 was high (ICC = 0.9, 95% CI = 0.87-0.92, p < 0.001, bias ± SD = 0.7 ± 6.1 events/h). Agreement values for OSA diagnosis (77-85%) between devices were similar to those seen from night-to-night variability of OSA using a single device. Awake baseline O2 saturation was significantly higher in the ARES™ (96.2 ± 1.6%) than WristOx2™ (92.2 ± 2.1%, p < 0.01). There was a significantly lower %time < 90%O2Sat reported by the ARES™ compared to WristOx2 (median (IQR) 0.5 (0.0, 2.6) vs. 2.1 (0.3, 9.7), p < 0.001), and the correlation was low (ICC = 0.2). CONCLUSIONS:OSA severity metrics predominantly dependent on change in oxygen saturation and metrics used in diagnosis of OSA (AHI4 and ODI) correlated well across devices tested. However, differences in cumulative oxygen desaturation measures (i.e., %time < 90%O2Sat) between the devices suggest that caution is needed when interpreting this metric particularly in populations likely to have significant hypoxia.
Project description:BackgroundMechanical ventilation via automated in-hospital ventilators is quite common during cardiopulmonary resuscitation. It is not known whether different inspiratory triggering sensitivity settings of ordinary ventilators have different effects on actual ventilation, gas exchange and hemodynamics during resuscitation.Methods18 pigs enrolled in this study were anaesthetized and intubated. Continuous chest compressions and mechanical ventilation (volume-controlled mode, 100% O2, respiratory rate 10/min, and tidal volumes 10ml/kg) were performed after 3 minutes of ventricular fibrillation. Group trig-4, trig-10 and trig-20 (six pigs each) were characterized by triggering sensitivities of 4, 10 and 20 (cmH2O for pressure-triggering and L/min for flow-triggering), respectively. Additionally, each pig in each group was mechanically ventilated using three types of inspiratory triggering (pressure-triggering, flow-triggering and turned-off triggering) of 5 minutes duration each, and each animal matched with one of six random assortments of the three different triggering settings. Blood gas samples, respiratory and hemodynamic parameters for each period were all collected and analyzed.ResultsIn each group, significantly lower actual respiratory rate, minute ventilation volume, mean airway pressure, arterial pH, PaO2, and higher end-tidal carbon dioxide, aortic blood pressure, coronary perfusion pressure, PaCO2 and venous oxygen saturation were observed in the ventilation periods with a turned-off triggering setting compared to those with pressure- or flow- triggering (all P<0.05), except when compared with pressure-triggering of 20 cmH2O (respiratory rate 10.5[10/11.3]/min vs 12.5[10.8/13.3]/min, P = 0.07; coronary perfusion pressure 30.3[24.5/31.6] mmHg vs 27.4[23.7/29] mmHg, P = 0.173; venous oxygen saturation 46.5[32/56.8]% vs 41.5[33.5/48.5]%, P = 0.575).ConclusionsVentilation with pressure- or flow-triggering tends to induce hyperventilation and deteriorating gas exchange and hemodynamics during CPR. A turned-off patient triggering or a pressure-triggering of 20 cmH2O is preferred for ventilation when an ordinary inpatient hospital ventilator is used during resuscitation.
Project description:IntroductionSodium thiosulfate (Na2S2O3), an H2S releasing agent, was shown to be organ-protective in experimental hemorrhage. Systemic inflammation activates immune cells, which in turn show cell type-specific metabolic plasticity with modifications of mitochondrial respiratory activity. Since H2S can dose-dependently stimulate or inhibit mitochondrial respiration, we investigated the effect of Na2S2O3 on immune cell metabolism in a blinded, randomized, controlled, long-term, porcine model of hemorrhage and resuscitation. For this purpose, we developed a Bayesian sampling-based model for 13C isotope metabolic flux analysis (MFA) utilizing 1,2-13C2-labeled glucose, 13C6-labeled glucose, and 13C5-labeled glutamine tracers.MethodsAfter 3 h of hemorrhage, anesthetized and surgically instrumented swine underwent resuscitation up to a maximum of 68 h. At 2 h of shock, animals randomly received vehicle or Na2S2O3 (25 mg/kg/h for 2 h, thereafter 100 mg/kg/h until 24 h after shock). At three time points (prior to shock, 24 h post shock and 64 h post shock) peripheral blood mononuclear cells (PBMCs) and granulocytes were isolated from whole blood, and cells were investigated regarding mitochondrial oxygen consumption (high resolution respirometry), reactive oxygen species production (electron spin resonance) and fluxes within the metabolic network (stable isotope-based MFA).ResultsPBMCs showed significantly higher mitochondrial O2 uptake and lower O2•- production in comparison to granulocytes. We found that in response to Na2S2O3 administration, PBMCs but not granulocytes had an increased mitochondrial oxygen consumption combined with a transient reduction of the citrate synthase flux and an increase of acetyl-CoA channeled into other compartments, e.g., for lipid biogenesis.ConclusionIn a porcine model of hemorrhage and resuscitation, Na2S2O3 administration led to increased mitochondrial oxygen consumption combined with stimulation of lipid biogenesis in PBMCs. In contrast, granulocytes remained unaffected. Granulocytes, on the other hand, remained unaffected. O2•- concentration in whole blood remained constant during shock and resuscitation, indicating a sufficient anti-oxidative capacity. Overall, our MFA model seems to be is a promising approach for investigating immunometabolism; especially when combined with complementary methods.
Project description:ObjectivesLactate is a major parameter in medical decision making. During labor, it is an indicator for fetal acidosis and immediate intervention. In the Emergency Department (ED), rapid analysis of lactate/blood gas is crucial for optimal patient care. Our objectives were to cross-compare-for the first time-two point-of-care testing (POCT) lactate devices with routine laboratory results using novel tight precision targets and evaluate different lactate cut-off concentrations to predict metabolic acidosis.Design and methodsBlood samples from the delivery room (n=66) and from the ED (n=85) were analyzed on two POCT devices, the StatStrip-Lactate (Nova Biomedical) and the iSTAT-1 (CG4+ cassettes, Abbott), and compared to the routine laboratory analyzer (ABL-735, Radiometer). Lactate concentrations were cross-compared between these analyzers.ResultsThe StatStrip correlated well with the ABL-735 (R=0.9737) and with the iSTAT-1 (R=0.9774) for lactate in umbilical cord blood. Lactate concentrations in ED samples measured on the iSTAT-1 and ABL-735 showed a correlation coefficient of R=0.9953. Analytical imprecision was excellent for lactate and pH, while for pO2 and pCO2 the coefficient of variation was relatively high using the iSTAT-1.ConclusionBoth POCT devices showed adequate analytical performance to measure lactate. The StatStrip can indicate metabolic acidosis in 1 μl blood and will be implemented at the delivery room.
Project description:BackgroundTo determine if a method for irrigation and aspiration (I/A) during cataract surgery provides effective removal of ophthalmic viscoelastic device (OVD).MethodsJapanese porcine eyes were used to evaluate I/A performance with Technique 1 (the I/A tip placed on the center of the anterior surface of the IOL), Technique 2 (the I/A tip alternately pressed near the edge of the IOL optic anterior surface on one side and then the other to tilt the IOL back and forth), and Technique 3 (the I/A tip inserted behind the IOL optic, between it and the posterior capsule). Techniques 1 and 2 were compared using the Miyake-Apple posterior view video technique to visualize the flow of irrigation fluid containing triamcinolone acetonide particles behind the IOL. To check the efficacy of OVD removal from behind the IOL for of all three I/A techniques, OVD with fluorescein beads were inserted inside the lens capsule before implantation of the IOL. After each I/A technique, eyes were prepared for Miyake-Apple viewing and pictures of the lens capsule were taken using fluorescent microscopy. Residual fluorescein beads in the capsular bag were analyzed.ResultsTechnique 1 resulted in a straight flow of fluid behind the IOL, while Technique 2 resulted in a vortex flow. The average amount of OVD retained inside the capsule after using Technique 2 or 3 was significantly lower than after using Technique 1 (p <0.0001).ConclusionsTechnique 2 proved to remove more effectively fluorescein bead-labelled OVD under the IOL than Technique 1.
Project description:IntroductionNewborn resuscitation is commonly performed in the presence of face mask leak. Leak is highly variable, pressure-dependent and often unrecognized. The effectiveness of resuscitation devices to deliver adequate inflations in the presence of leak is unknown. Bench models simulating continuous leak have the disadvantage of not accurately reflecting leak occurring during clinical resuscitation. A dynamic leak model based on pressure-release valves was thus developed.MethodsThis study investigates self-inflating bag (SIB) and T-piece resuscitator (TPR) ventilation performance in the presence of dynamic (DLM) compared to continuous (CLM) leak models in a bench study. Five predefined leak levels were tested for each leak model (0%-87%). Resuscitation devices were connected to a test lung (compliance 0.6 mL/cmH2O) and respiratory parameters were measured using respiratory function monitors before (patient interface) and after (actual) an induced leak at 40, 60, 80 inflations/min.ResultsThree thousand six hundred inflations were analyzed. DLM showed a decrease in actual tidal volumes from 0%-87% leak with tidal volume differences (SIB 4.8 mL, TPR 2.9 mL), contrasting to minimal change for CLM (SIB -0.6 mL, TPR 0.3 mL). CLM demonstrated larger differences between patient interface and actual leak. The absolute difference at 60 inflations/min at 87% leak were SIB 37.5%, TPR 18.2% for CLM compared to SIB 4.6%, TPR 1.4% for DLM.ConclusionsCLM may underestimate the impact of resuscitation device performance with poor correlation between patient interface and actual delivered volume. DLM demonstrates several advantages with a more accurate representation of face mask leak and will prove useful in modeling all systems delivering PPV.
Project description:BackgroundFast and effective treatment of hemorrhagic shock is one of the most important preclinical trauma care tasks e.g., in combat casualties in avoiding severe end-organ damage or death. In scenarios without immediate availability of blood products, alternate regimens of fluid resuscitation represent the only possibility of maintaining sufficient circulation and regaining adequate end-organ oxygen supply. However, the fluid choice alone may affect the extent of the bleeding by interfering with coagulation pathways. This study investigates the impact of hydroxyethyl starch (HES), gelatine-polysuccinate (GP) and balanced electrolyte solution (BES) as commonly used agents for fluid resuscitation on coagulation using a porcine hemorrhagic shock model.MethodsFollowing approval by the State and Institutional Animal Care Committee, life-threatening hemorrhagic shock was induced via arterial blood withdrawal in 24 anesthetized pigs. Isovolumetric fluid resuscitation with either HES, GP or BES (n = 3 × 8) was performed to compensate for the blood loss. Over four hours, hemodynamics, laboratory parameters and rotational thromboelastometry-derived coagulation were analyzed. As secondary endpoint the porcine values were compared to human blood.ResultsAll the agents used for fluid resuscitation significantly affected coagulation. We measured a restriction of laboratory parameters, clot development and clot firmness, particularly in HES- and GP-treated animals. Hemoglobin content dropped in all groups but showed a more pronounced decline in colloid-treated pigs. This effect was not maintained over the four-hour monitoring period.ConclusionHES, GP, and BEL sufficiently stabilized the macrocirculation, but significantly affected coagulation. These effects were most pronounced after colloid and particularly HES administration. Despite suitability for rapid hemodynamic stabilization, colloids have to be chosen with caution, because their molecular properties may affect coagulation directly and as a consequence of pronounced hemodilution. Our comparison of porcine and human coagulation showed increased coagulation activity in pig blood.